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Cancer Associated Thrombosis, a Pilot Treatment Study Using Rivaroxaban (CASTA-DIVA)

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ClinicalTrials.gov Identifier: NCT02746185
Recruitment Status : Completed
First Posted : April 21, 2016
Last Update Posted : August 13, 2018
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE December 15, 2015
First Posted Date  ICMJE April 21, 2016
Last Update Posted Date August 13, 2018
Actual Study Start Date  ICMJE September 2016
Actual Primary Completion Date April 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
  • Symptomatic DVT [ Time Frame: 3 months ]
    Recurrent VTE during the 3-month treatment period including all symptomatic DVT (lower limbs distal and proximal DVTs, iliac and caval thrombosis, visceral thrombosis and deep vein thrombosis of the arm)
  • Symptomatic PE [ Time Frame: 3 months ]
    Recurrent VTE during the 3-month treatment period including symptomatic PE
  • Unsuspected PE and DVT [ Time Frame: 3 months ]
    Recurrent VTE during the 3-month treatment period including clinically unsuspected PE and DVT discovered incidentally
  • Worsening of pulmonary vascular or venous obstruction [ Time Frame: 3 months ]
    Recurrent VTE during the 3-month treatment period including worsening of pulmonary vascular obstruction or venous obstruction on the systematic examinations performed at the end of the 3-month treatment period
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2016)
  • Major and clinically significant bleedings during the 3-month treatment period [ Time Frame: 3 months ]
    Major bleeding is defined according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and includes any bleeding resulting in death; symptomatic bleeding in a critical organ including intracranial, intra spinal, intraocular, retroperitoneal, intra articular and pericardial bleeding and muscle bleeding resulting in compartment syndrome; symptomatic bleeding resulting in a decrease in the hemoglobin concentration of at least 2g/dL or resulting in the transfusion of at least two packs of blood red cells.
  • Symptomatic recurrences of PE or DVT of the legs [ Time Frame: 3 months ]
    excluding visceral thrombosis, upper extremity deep vein thrombosis and clinically unsuspected PE and DVT diagnosed incidentally
  • Major and non-major clinically significant bleedings at day 90 [ Time Frame: 3 months ]
    Clinically significant non-major bleedings are defined as any bleeding requiring hospitalization or a medical intervention including temporary withholding of anticoagulant treatment to stop bleeding.
  • Mortality [ Time Frame: 3 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: April 18, 2016)
Rivaroxaban plasma concentrations [ Time Frame: 3 months ]
Area under the plasma concentration versus time curve (AUC) determined using a liquid chromatography-tandem mass spectrometry method
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Cancer Associated Thrombosis, a Pilot Treatment Study Using Rivaroxaban
Official Title  ICMJE Efficacy and Safety of Oral Rivaroxaban for the Treatment of Venous Thromboembolism in Patients With Active Cancer. A Pilot Study.
Brief Summary The study will compare the efficacy and safety of oral rivaroxaban and subcutaneous dalteparin in patients with cancer associated thrombosis. It is designed as a non-inferiority open label randomized multicenter trial with blinded adjudication of outcome events.
Detailed Description Patients with active cancer and symptomatic pulmonary embolism, proximal deep vein thrombosis, iliac or caval thrombosis will be randomly assigned to receive either dalteparin using the CLOT regimen or to oral rivaroxaban using the conventional dosage given in the Einstein studies. Experimental and control treatments will be given for three months. The main outcome at three month will include all symptomatic and incidentally discovered venous thromboembolic events including pulmonary embolism (either objectively confirmed and death due to pulmonary embolism), lower limb and upper limb deep vein thrombosis, iliac, caval and visceral thrombosis and any worsening of vascular obstruction which will be collected systematically at inclusion and at day 90. The safety end-points will consist of the rate of major bleedings and the composite of major and non-major but clinically significant bleedings at day 90. All outcome events will be blindly adjudicated by a central independent adjudication committee.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Neoplasm
  • Venous Thromboembolism
Intervention  ICMJE
  • Drug: rivaroxaban
    rivaroxaban, 15 mg BD (Bis in die) for 3 weeks followed by 20mg OD (Omni die) for 9 weeks
    Other Name: xarelto
  • Drug: Low-molecular-weight heparin
    dalteparin, 200 IU/kg OD for 4 weeks followed by 150 IU/kg OD for 8 weeks
    Other Name: dalteparin
Study Arms  ICMJE
  • Active Comparator: Low-molecular-weight heparin
    dalteparin, 200 IU/kg subcutaneously once daily for one month followed by 150 IU/kg subcutaneously once daily for 2 months
    Intervention: Drug: Low-molecular-weight heparin
  • Experimental: Rivaroxaban
    rivaroxaban, orally, 15 mg twice daily for 3 weeks followed by 20 mg once daily for 9 weeks
    Intervention: Drug: rivaroxaban
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 15, 2018)
159
Original Estimated Enrollment  ICMJE
 (submitted: April 18, 2016)
200
Actual Study Completion Date  ICMJE April 25, 2018
Actual Primary Completion Date April 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age > 18 years
  • Social security affiliation
  • Written informed consent
  • Solid active cancer, high grade lymphoma or myeloma treated with Immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide). Active cancer is defined as the presence of measurable disease or ongoing (or planned) chemotherapy, radiotherapy or targeted therapy at inclusion.
  • Histologically or cytologically proven cancer.
  • Symptomatic venous thromboembolism objectively confirmed diagnosed because of symptoms or discovered incidentally
  • High-risk of recurrent Venous thromboembolism (VTE) defined by a score of 0 or ≥ 1, using the following criteria: female sex (+1), lung cancer (+1), breast cancer (-1) non metastatic tumor (-2), previous VTE (+1).

Exclusion Criteria:

  • Exclusive adjuvant hormonal treatment with no measurable residual disease
  • Sub-segmental isolated pulmonary embolism (PE) without associated proximal DVT
  • Isolated distal deep vein thrombosis (DVT) of the legs
  • Isolated upper-extremity DVT or superior vena cava thrombosis
  • Isolated visceral thrombosis
  • Platelet count < 50 000 G/L
  • Active bleeding
  • Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C
  • Hemostatic defect with contraindication to anticoagulant treatment at therapeutic dosage
  • Vena cava filter at inclusion
  • Fibrinolytic therapy within 3 days preceding inclusion
  • Creatinine clearance < 30 ml/min according to Cockcroft-Gault formula
  • Previous heparin-induced thrombocytopenia
  • Anticoagulant treatment at curative dosage for more than 3 days before inclusion
  • Pregnancy or lack of effective contraceptive treatment for women of childbearing age
  • Treatment with both strong CYP3A4 and P-glycoprotein (PgP) inhibitors: protease inhibitors for HIV disease, systemic ketoconazole
  • Treatment with a strong CYP3A4 inducer: rifampicin, carbamazepine, phenytoin.
  • Life expectancy < 3 months
  • Eastern Cooperative Oncology Group (ECOG) level 3 or 4
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02746185
Other Study ID Numbers  ICMJE P141204
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Bayer
Investigators  ICMJE
Principal Investigator: Guy Meyer, MD APHP - HEGP
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP